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Papers by JOSE MANUEL MARTIN VILLA

Research paper thumbnail of Major histocompatibility complex complement (MHC) Bf alleles show trans species evolution between man and chimpanzee

Scientific Reports

HLA and disease studies by using single allele statistics have been fruitless during the last 40 ... more HLA and disease studies by using single allele statistics have been fruitless during the last 40 years for explaining association pathogenesis of the associated diseases.Other approaches are necessary to untangle this puzzle. We aim to revisit complement alleleism in humans and primates for both studying MHC and disease association to complotypes and extended MHC haplotypes in order to also explain the positive directional selection of maintaining immune response genes (complement, MHC adaptive and MHC non-specific genes) that keeps these three type of genes together in a short chromosome stretch (MHC) for million years. These genes may be linked to conjointly avoid microbes attack and autoimmunity. In the present paper, it is obtained a new Bf chimpanzee allele, provisionaly named Patr-Bf*A:01,that differs from other Bf alleles by having CTG at eleventh codon of exon 2 in order to start the newly suggested methodology and explain functional and evolutionary MHC obscure aspects. Exo...

Research paper thumbnail of HLA alleles and haplotypes in Sudanese population and their relationship with Mediterraneans

Scientific Reports

The contribution of migrated people from once green Sahara (about 10,000–6000 years bc) towards M... more The contribution of migrated people from once green Sahara (about 10,000–6000 years bc) towards Mediterranean area had probably a double effect: both genetic and cultural connections have been described between Western Europe and North Africa. Sudanese populations from different ethnicities have been studied for HLA-A, -B, -DRB1 and -DQB1 antigens by a standard microlymphotoxicity method. Results found show that Nubians are genetically related with African Sub-Saharan populations and distant from other Sudanese tribes, who are closer to Mediterranean populations than to Sub-Saharan ones. This is concordant with other authors and meta-analysis data. Our present work is, to our knowledge, the first and only one HLA research that studies Sudanese people according to different Sudan ethnic groups: samples were collected before Sudan partition between North and South. A prehistoric genetic and peoples exchange between Africa and the Mediterranean basin may be observed and is supported wi...

Research paper thumbnail of HLA study in Mexico Nahua/Aztec Amerindians: Close relatedness to the ancient Central America ethnic groups

Human Immunology

Nahua population (also named Aztecs or Mexicas) were studied for HLA class II genes in a Mexican ... more Nahua population (also named Aztecs or Mexicas) were studied for HLA class II genes in a Mexican rural city (Santo Domingo Ocotitlan, Morelos State) belonging to the nowadays Náhuatl speaking areas in Mexico. The most frequent HLA class II alleles were typical Amerindian (HLA-DRB1*04:07, DQB1*03:01 DRB1*04:03 or DRB1*04:04) and also were some calculated extended haplotypes (HLA-DRB1*04:07-DQB1*03:02,DRB1*08:02-DQB1*04:02, or DRB1*10:01-DQB1*05:01 among others). When using HLA-DRB1 Neís genetic distances, our isolated Nahua population was found to be close to other Central America Amerindians like the ancientestablished Mayans or Mixe. This may suggest that Nahuas origin was also from Central America. In contrast to legend that says they came from the North, and they built the Aztec Empire after submitting neighbouring ethnic groups before 1521 CE when Spaniards led by Hernán Cortés arrived to Mexico.

Research paper thumbnail of Propuesta de mejora del Sistema Interno de Garantía de Calidad de la Facultad de Medicina

La garantia de calidad en el ambito universitario puede considerarse como la atencion sistematica... more La garantia de calidad en el ambito universitario puede considerarse como la atencion sistematica, estructurada y continua a las titulaciones ofertadas. La garantia de calidad se compromete a poner en marcha los medios que aseguren y demuestren la calidad de los programas formativos que se desarrollan en cada una de las titulaciones ofrecidas por la Universidad y asi cumplir con la obligacion que tiene con la sociedad. El presente proyecto nace como fruto de la responsabilidad adquirida para el cumplimiento de las funciones encomendadas y, con el objetivo de seguir adoptando una estrategia de mejora continua de la calidad de la docencia y satisfaccion de los colectivos implicados en el proceso de ensenanza-aprendizaje (Profesorado, Estudiantes y PAS).

Research paper thumbnail of HLA‐G in Mayas from Yucatan: An evolutionary approach

International Journal of Immunogenetics, 2021

HLA‐G allele frequencies were studied in Yucatán (Mexico) Maya Amerindians by a direct exon DNA s... more HLA‐G allele frequencies were studied in Yucatán (Mexico) Maya Amerindians by a direct exon DNA sequencing technique. It is described that Mayas are probably one of the first populations together with Olmecs that populated Meso America and that important HLA genetic differences between Mexican and Guatemalan Mayas support that Maya languages were imposed to several neighbouring Amerindian groups. HLA‐G*01:01:02, HLA‐G*01:01:01 and HLA‐G*01:04:01 are the most frequent alleles in this population. It is remarkable that HLA‐G*01:05N allele was not found in the population in accordance with similar results found in another Amerindians. Also, protein allele HLA‐G*01:04 frequency is found not to differ to those found in another far or close living Amerindians in contrast to other World populations. It seems that while high HLA‐G*01:05N frequency is found in Iran and Middle East populations, probably where this allele appeared within an ancestral HLA‐A*19 group of alleles haplotype and it is maintained by unknown evolutionary forces, Amerindians do not have a high frequency because a founder effect or because required natural evolutionary forces do not exist in America. Finally, we believe useful to study HLA‐G evolution for its physiopathology understanding in addition to the many papers on statistics on HLA‐G and in vitro models that are yearly published.

Research paper thumbnail of HLA genetic study from United Arab Emirates (UAE), Abu Dhabi

Human Immunology, 2019

Emiratis belong to the United Arab Emirates (UAE) country. UAE is placed at the East part of the ... more Emiratis belong to the United Arab Emirates (UAE) country. UAE is placed at the East part of the Arabian Peninsula, protruding into the Arabia Gulf and was populated since 130,000 years ago. First humans migrating out of Africa went probably across this territory. HLA-A,-B,-C,-DRB1,-DQB1,-DQA1 were typed in order to obtain HLA profile for clinical, epidemiological and population genetics studies. Twenty different HLA-A, thirtyfive HLA-B and twenty-two HLA-C class I alleles were detected; twenty-seven different HLA-DRB1, fourteen HLA-DQB1 and twelve HLA-DQA1 class II alleles were found. Most frequent extended HLA haplotypes are also depicted. People are present in this area since prehistoric ages according to archaeological studies; the "Out of Africa" eastern migration may have affected the present day population composition.

Research paper thumbnail of Major Histocompatibility Complex Allele Persistence in Eurasia and America in the Genus Carduelis (Spinus) During Million Years

The Open Ornithology Journal, 2017

Introduction:GenusCarduelis(Fringillidaefamily) includes goldfinches, siskins, redpolls, greenfin... more Introduction:GenusCarduelis(Fringillidaefamily) includes goldfinches, siskins, redpolls, greenfinches and crossbills. Many of the species classified within this genus and other related genera have been grouped by using molecular systematics and the mitochondrial cytochrome b (mt cyt b) gene. According to this, the Eurasian siskin (C. spinus)is the only one extant direct ancestor of several North American finches; North American / South American radiations may have been originated by Eurasian siskin (or extinct relative). In the present work, we aim to perform a study of transpecies and transcontinental analyses of MHC (Major Histocompatibility Complex) Class I alleles in several genusCarduelis/Spinusspecies in order to draw evolutionary conclusions in several wild bird species belonging to the genusCarduelis / Spinus.Materials and Methods:Blood was taken from worldwide wild bird species. Passerine phylogeny was done after analysing mtDNA with Maximun Likelihood and Bayesian dendrogr...

Research paper thumbnail of Programmed Cell Death 1 and Helios Distinguish TCR-αβ+ Double-Negative (CD4-CD8-) T Cells That Derive from Self-Reactive CD8 T Cells

Journal of immunology (Baltimore, Md. : 1950), Jan 30, 2015

TCR-αβ(+) double-negative (DN; CD4(-)CD8(-)) T cells represent a poorly understood cellular subse... more TCR-αβ(+) double-negative (DN; CD4(-)CD8(-)) T cells represent a poorly understood cellular subset suggested to contribute to the pathogenesis of the autoimmune disease systemic lupus erythematosus. DN T cells have been proposed to derive from CD8(+) cells. However, the conditions that govern the loss of CD8 expression after Ag encounter are unknown. In this study, we tracked the fate of CD8 T cells from transgenic TCR mice exposed to their cognate Ags as self or in the context of infection. We demonstrate that CD8 T cells lose CD8 expression and become DN only when cognate Ag is sensed as self. This process is restricted to tissues where the Ag is present. We also show that DN T cells derived from self-reactive CD8 cells express the inhibitory molecules PD-1 and Helios. These molecules identify a subset of DN T cells in normal mice. A similar population expands when CD8 T cells from repertoires enriched in self-reactive cells (Aire-deficient) are transferred into cognate hosts. Col...

Research paper thumbnail of Cyclic Expression of HLA Class I and II Molecules on the Surface of Purified Human Spermatozoa and Their Control by Serum Inhibin B Levels

Biology of Reproduction, 1999

HLA class I and class II expression was analyzed weekly by cytofluorometry on spermatozoa samples... more HLA class I and class II expression was analyzed weekly by cytofluorometry on spermatozoa samples from four donors during a 15-wk trial. On the same day that semen samples were studied, and to analyze whether this expression was hormonecontrolled, serum levels of testosterone, LH, FSH, inhibin B, activin, and pro-␣C on the one hand, and seminal plasma levels of inhibin B, activin, and ␣-inhibin on the other, were also measured. Inhibin B and related peptides were quantitated using a novel two-site assay with monoclonal antibodies to the ␣ and ␤ subunits of inhibin. Our results showed that HLA class I and class II molecules were expressed on the spermatozoa's surface, following a cyclic pattern, and that there was a simultaneous and coordinated expression of both types of molecules (r ‫؍‬ 0.801, P Ͻ 0.0001). Furthermore, when the expression of these molecules was plotted against the different hormone levels, serum inhibin B showed a clear inverse correlation with HLA class I (r ‫؍‬ Ϫ0.612, P Ͻ 0.0001) and class II (r ‫؍‬ Ϫ0.534, P Ͻ 0.0001). This finding reveals unexpected functions of inhibin B, which may be relevant in the fertilization process and on male fertility control.

Research paper thumbnail of HLA-G: Too Much or Too Little? Role in Cancer and Autoimmune Disease

Frontiers in Immunology, 2022

HLA-G is a non-classical HLA class I molecule with immunomodulatory properties. It was initially ... more HLA-G is a non-classical HLA class I molecule with immunomodulatory properties. It was initially described at the maternal-fetal interface, and it was later found that this molecule was constitutively expressed on certain immuneprivileged tissues, such as cornea, endothelial and erythroid precursors, and thymus. The immunosuppressive effect of HLA-G is exerted through the interaction with its cognate receptors, expressed on immunocompetent cells, like ILT2, expressed on NK, B, T cells and APCs; ILT4, on APCs; KIR, found on the surface of NK cells; and finally, the co-receptor CD8. Because of these immunomodulatory functions, HLA-G has been involved in several processes, amongst which organ transplantation, viral infections, cancer progression, and autoimmunity. HLA-G neo-expression on tumors has been recently described in several types of malignancies. In fact, tumor progression is tightly linked to the presence of the molecule, as it exerts its tolerogenic function, inhibiting the ...

Research paper thumbnail of Origin of Azeris (Iran) according to HLA genes

International Journal of Modern Anthropology, 2017

Azeris from Iran North West provinces (Tabriz city) have been studied for HLA alleles. A total of... more Azeris from Iran North West provinces (Tabriz city) have been studied for HLA alleles. A total of 8.902 HLA-bearing chromosomes (Chr 6) have been used for comparing their relatedness with other Middle East, Caucasus, Mediterranean and Central Asia populations. Mediterranean, Central Asian and Caucasus extended HLA haplotypes were found, i.e.: A*24:02-B*35:01-DBR1*11:01-DBQ1*03:01 and A*01:02-B*08:01-DRB1*03:01-DQB1*02:01. Genetic distances, Neighbour Joining and Correspondence analyses also showed that Azeris were close to Kurds, who have shown a closer Mediterranean/Caucasus HLA profile, and Gorgan (Turkmen) who have shown a closer Central Asia profile, as expected. It is shown that three different Iranian populations according to Language, History and Geography: Gorgans, Kurds and Azeris are genetically close. In fact, old Azeri language (Adari) was an Iranian language and not a Turkic one, which they nowadays speak. Also, present study does not support "Aryan" invasion from the East in accordance with many other previous studies. Finally, our results are useful for establishing Preventive Medicine programs in Transplantation and HLA and Pharmacogenomics/Disease linkage.

Research paper thumbnail of A Reliable and Standardizable Differential PCR and qPCR Methodology Assesses HER2 Gene Amplification in Gastric Cancer

Biology, 2021

Simple Summary Patients with gastric cancer may present variations in the copy number of the HER2... more Simple Summary Patients with gastric cancer may present variations in the copy number of the HER2 gene in their primary tumors. The techniques used to detect these variations and HER2 overexpression render false positive and negative results with high frequency, and robust methodologies are required to assess this amplification and confidently select patients who may benefit from HER2-specific monoclonal antibody-based therapies. We addressed this issue by molecular biology techniques using DNA samples from tumor or distal tissue of gastric cancer patients. The HER2 and a control (IFNG) gene were subjected to differential (diffPCR) and quantitative PCR (qPCR). A cut-off point above which patients can be deemed positive was set based on the HER2/IFNG ratio, achieved using DNA from 30 healthy donors. Both, diffPCR and qPCR, identified the presence of somatic HER2 amplifications in 25% of patients in DNA from tumoral tissue, but not distal, paired tissue samples. Immunohistochemistry a...

Research paper thumbnail of HLA genes in Chimila Amerindians (Colombia), the Peopling of America and Medical implications

International Journal of Modern Anthropology, 2016

Our aim is to study the HLA-A, -B, -C, -DRB1 and -DQB1 gene frequencies in the Chimila Amerindian... more Our aim is to study the HLA-A, -B, -C, -DRB1 and -DQB1 gene frequencies in the Chimila Amerindian (Colombia) ethnic group. Results are compared with other World populations in order to obtain information about Chimila and Amerindian Health promotion, Amerindian origins and America peopling. Written consent was obtained from Chimila subjects to be included in this study. Peripheral blood was drawn and HLA DNA genotyping was carried out by standard methods. Analyses of Chimila relatedness with other Amerindians and worldwide populations was performed with a standard NJ dendrogram and correspondence analyses methodology. Chimila HLA gene profile showed to be related to that of other Amerindians groups. New complete HLA extended haplotypes were obtained. Some of them are described for the first time. Also, specific genealogical comparisons were done between Chimila Amerindians and Pacific Islanders by using specific HLA alleles. Our conclusions are: 1) These new data and HLA extended ha...

Research paper thumbnail of Kurds HLA Genes: Its Implications in Transplantation and Pharmacogenomics

Open Medicine Journal, 2015

HLA genes (class I and II) have been studied in a Kurd population from Iran (North West towns of ... more HLA genes (class I and II) have been studied in a Kurd population from Iran (North West towns of Saqqez and Baneh, close to Irak border). Kurds speak an Iranian language. HLA Kurd profile has been compared with those of Central Asians, Siberians, Mediterraneans and other worldwide populations; a total of 7746 chromosomes were used for computer comparisons. Both Neighbor-joining and correspondence genetic analyses place Kurds in the Mediterranean population cluster, close to Iranians, Europeans and Caucasus populations (Svan and Georgian). New extended HLA haplotypes are described, being A*02:01-B*35:01-DRB1*01:01-DQB1*05:01 and A*24:02-B*18:09-DRB1*11:01- DQB1*03:01 the most frequent ones; other Kurd extended haplotypes are also found in Azeris and Palestinians. This research work may be useful for: 1) future Iranian Kurds transplantation regional programs, 2) HLA pharmacogenomics in order to practise a preventive Medicine and drug side effects, and 3) Epidemiology of HLA-associated...

Research paper thumbnail of HLA-G in Amerindians: Epidemiology and Worldwide Population Comparison

Open Medicine Journal, 2018

Background:HLA-G molecules are immunosuppressive and avoid fetal rejection by giving negative sig... more Background:HLA-G molecules are immunosuppressive and avoid fetal rejection by giving negative signals to maternal immune system from fetal trophoblast cell surface. HLA-G genes have been associated to different pathologies: Spontaneous abortions, autoimmunity, tumor progression, transplant rejection and infection. In addition, different World populations show remarkable different HLA-G allele frequencies in the allele that does not produce a full HLA-G molecule (HLA-G*05N); this allele is almost absent in studied Amerindians.Objectives:The aim is to study HLA-A.-B,-DRB1 and –G alleles and extended haplotypes in Amerindians for the first time. This may be useful to asses HLA-G epidemiology, association to disease and Preventive Medicine in Amerindians.Methods:HLA-A,-B and -DRB1 have been typed by using standard automatic protocols. HLA-G alleles have been detected by direct HLA-G exon 2, exon 3 and exon 4 DNA sequencing. Computer calculations have been done by specific standard metho...

Research paper thumbnail of Hla in colombia wayu from guajira peninsula amerindians: pacific ocean relationships

Research paper thumbnail of Hla in uros from peru titikaka lake uros: tiwanaku, easter and pacific islanders

Research paper thumbnail of The first free Africans in America: HLA study in San Basilio de Palenque (Colombia)

Human immunology, 2018

Original San Basilio de Palenque population (North Colombia) fled from Spanish traders that carri... more Original San Basilio de Palenque population (North Colombia) fled from Spanish traders that carried them as slaves and they funded in nearby Maria Mountains a fortified town (Palenque). They started helping new Africans brought as slaves to flee and join them. Most of them spoke a Bantu-Congo language and nowadays they speak the only one extant Bantu-Spanish Creole language. Spanish Crown was forced to issue a decree declaring them free (1691 CE), more than 100 years before than Haiti Republic existed. HLA-A, -B, -DRB1 and -DQB1 alleles were studied and further computer procedures were performed with Arlequin 3.5 software. No Amerindian or Europeans gene flow to this population was found. However, three specific HLA extended haplotypes are found in this population, which may reflect an isolation from other Africans or Afro-Americans also. This may be due to the maintenance of their own African culture, and even their unique Creole language.

Research paper thumbnail of HLA genes in Atlantic Celtic populations: are Celts Iberians?

International Journal of Modern Anthropology, 2017

Atlantic Europe populations were analyzed with HLA genes in order to establish their relationship... more Atlantic Europe populations were analyzed with HLA genes in order to establish their relationship among themselves and with other populations. Standard genetic and statistical software analyses were used. Celtic populations (British Isles and French Bretons) have genetically been found close together: Irish, Welsh, Orkney Islanders (Scottish), French Bretons, Galicians, Spanish Basques, Portuguese, cluster together in DA genetic distances, correspondence analysis and Neighbour Joining dendrograms. Genetics have been shown by itself not suffice to determine populations migration/relatedness. Aristotle and Herodotus placed Celts in Iberia and R1b chromosome Y marker is high in Iberia and all Celtic European populations above mentioned (probably stemming from Iberian Ice refugee after Last Glaciation) and Ancient Celt language (Gaelic) is being translated from Iberian-Tartesian language: these suggest that Celts and Iberians, so named by Classic authors, constitute the same population. On the other hand, a) R1b gene analysis of Canary Islands ancient inhabitants (Guanches), b) abundant Iberian scripts are also found in Canary Islands, c) a established North Africa/Iberia ancient gene flow, and d) no evidence of demic diffusion from eastern to western Mediterranean according to human ancient skeleton studies is noticed in Mesolithic/Neolithic transition: these facts suggest that ancient Canary Islanders may be included within the Iberian/Celtic population. Our conclusions are that: 1) Celts are concentrated in Atlantic Europe, 2) Iberians and Celts mentioned by classic authors most probably refer to the same population living in Iberian Peninsula (Spain/Portugal); in addition, North African Berbers and ancient Canary Islanders also belong to this group 3) Postulated farmers demic diffusion in a East to West Mediterranean direction never existed.

Research paper thumbnail of Origin of Ancient Canary Islanders Guanches: presence of Atlantic/Iberian HLA and Y chromosome genes and Ancient Iberian language

International Journal of Modern Anthropology, 2015

First Canary Islands (Spain) Inhabitants ("Guanches") origin has been much debated. Lately, it ha... more First Canary Islands (Spain) Inhabitants ("Guanches") origin has been much debated. Lately, it has come popular the simplistic theory that they came from North Africa. In the present paper, we conclude that not only North Africans but also Iberian/Atlantic Europeans (and possibly others) must have been first Canarians. Debate whether North Africans or Iberians were the first "Guanches" is artificial since Iberian Peninsula-North African genes flow in ancient times was abundant and Iberians share a great part of genetic profile with North Africans. New genetic (HLA) and linguistic data shown in the present paper is conjointly analyzed with early anthropological data; at least two "Guanches" anthropological types existed. In addition, a correct interpretation of R1b Y chromosome high frequency in Atlantic Europe (Ireland, British Isles, North Spain and Portugal), which is also found in Canary Islands (13.3%) supports that Atlantic/Europeans are among Canary Islands First Inhabitants. Present paper HLA genes partial data and presence of abundant old Iberian language scripts (which show an easy translation proposal by using Basque language) suggest that a present day dogma of a hypothetically North African single origin should be changed. Both Atlantic/Europeans and North Africans must have been in the origin of Canary Islands First Inhabitants.

Research paper thumbnail of Major histocompatibility complex complement (MHC) Bf alleles show trans species evolution between man and chimpanzee

Scientific Reports

HLA and disease studies by using single allele statistics have been fruitless during the last 40 ... more HLA and disease studies by using single allele statistics have been fruitless during the last 40 years for explaining association pathogenesis of the associated diseases.Other approaches are necessary to untangle this puzzle. We aim to revisit complement alleleism in humans and primates for both studying MHC and disease association to complotypes and extended MHC haplotypes in order to also explain the positive directional selection of maintaining immune response genes (complement, MHC adaptive and MHC non-specific genes) that keeps these three type of genes together in a short chromosome stretch (MHC) for million years. These genes may be linked to conjointly avoid microbes attack and autoimmunity. In the present paper, it is obtained a new Bf chimpanzee allele, provisionaly named Patr-Bf*A:01,that differs from other Bf alleles by having CTG at eleventh codon of exon 2 in order to start the newly suggested methodology and explain functional and evolutionary MHC obscure aspects. Exo...

Research paper thumbnail of HLA alleles and haplotypes in Sudanese population and their relationship with Mediterraneans

Scientific Reports

The contribution of migrated people from once green Sahara (about 10,000–6000 years bc) towards M... more The contribution of migrated people from once green Sahara (about 10,000–6000 years bc) towards Mediterranean area had probably a double effect: both genetic and cultural connections have been described between Western Europe and North Africa. Sudanese populations from different ethnicities have been studied for HLA-A, -B, -DRB1 and -DQB1 antigens by a standard microlymphotoxicity method. Results found show that Nubians are genetically related with African Sub-Saharan populations and distant from other Sudanese tribes, who are closer to Mediterranean populations than to Sub-Saharan ones. This is concordant with other authors and meta-analysis data. Our present work is, to our knowledge, the first and only one HLA research that studies Sudanese people according to different Sudan ethnic groups: samples were collected before Sudan partition between North and South. A prehistoric genetic and peoples exchange between Africa and the Mediterranean basin may be observed and is supported wi...

Research paper thumbnail of HLA study in Mexico Nahua/Aztec Amerindians: Close relatedness to the ancient Central America ethnic groups

Human Immunology

Nahua population (also named Aztecs or Mexicas) were studied for HLA class II genes in a Mexican ... more Nahua population (also named Aztecs or Mexicas) were studied for HLA class II genes in a Mexican rural city (Santo Domingo Ocotitlan, Morelos State) belonging to the nowadays Náhuatl speaking areas in Mexico. The most frequent HLA class II alleles were typical Amerindian (HLA-DRB1*04:07, DQB1*03:01 DRB1*04:03 or DRB1*04:04) and also were some calculated extended haplotypes (HLA-DRB1*04:07-DQB1*03:02,DRB1*08:02-DQB1*04:02, or DRB1*10:01-DQB1*05:01 among others). When using HLA-DRB1 Neís genetic distances, our isolated Nahua population was found to be close to other Central America Amerindians like the ancientestablished Mayans or Mixe. This may suggest that Nahuas origin was also from Central America. In contrast to legend that says they came from the North, and they built the Aztec Empire after submitting neighbouring ethnic groups before 1521 CE when Spaniards led by Hernán Cortés arrived to Mexico.

Research paper thumbnail of Propuesta de mejora del Sistema Interno de Garantía de Calidad de la Facultad de Medicina

La garantia de calidad en el ambito universitario puede considerarse como la atencion sistematica... more La garantia de calidad en el ambito universitario puede considerarse como la atencion sistematica, estructurada y continua a las titulaciones ofertadas. La garantia de calidad se compromete a poner en marcha los medios que aseguren y demuestren la calidad de los programas formativos que se desarrollan en cada una de las titulaciones ofrecidas por la Universidad y asi cumplir con la obligacion que tiene con la sociedad. El presente proyecto nace como fruto de la responsabilidad adquirida para el cumplimiento de las funciones encomendadas y, con el objetivo de seguir adoptando una estrategia de mejora continua de la calidad de la docencia y satisfaccion de los colectivos implicados en el proceso de ensenanza-aprendizaje (Profesorado, Estudiantes y PAS).

Research paper thumbnail of HLA‐G in Mayas from Yucatan: An evolutionary approach

International Journal of Immunogenetics, 2021

HLA‐G allele frequencies were studied in Yucatán (Mexico) Maya Amerindians by a direct exon DNA s... more HLA‐G allele frequencies were studied in Yucatán (Mexico) Maya Amerindians by a direct exon DNA sequencing technique. It is described that Mayas are probably one of the first populations together with Olmecs that populated Meso America and that important HLA genetic differences between Mexican and Guatemalan Mayas support that Maya languages were imposed to several neighbouring Amerindian groups. HLA‐G*01:01:02, HLA‐G*01:01:01 and HLA‐G*01:04:01 are the most frequent alleles in this population. It is remarkable that HLA‐G*01:05N allele was not found in the population in accordance with similar results found in another Amerindians. Also, protein allele HLA‐G*01:04 frequency is found not to differ to those found in another far or close living Amerindians in contrast to other World populations. It seems that while high HLA‐G*01:05N frequency is found in Iran and Middle East populations, probably where this allele appeared within an ancestral HLA‐A*19 group of alleles haplotype and it is maintained by unknown evolutionary forces, Amerindians do not have a high frequency because a founder effect or because required natural evolutionary forces do not exist in America. Finally, we believe useful to study HLA‐G evolution for its physiopathology understanding in addition to the many papers on statistics on HLA‐G and in vitro models that are yearly published.

Research paper thumbnail of HLA genetic study from United Arab Emirates (UAE), Abu Dhabi

Human Immunology, 2019

Emiratis belong to the United Arab Emirates (UAE) country. UAE is placed at the East part of the ... more Emiratis belong to the United Arab Emirates (UAE) country. UAE is placed at the East part of the Arabian Peninsula, protruding into the Arabia Gulf and was populated since 130,000 years ago. First humans migrating out of Africa went probably across this territory. HLA-A,-B,-C,-DRB1,-DQB1,-DQA1 were typed in order to obtain HLA profile for clinical, epidemiological and population genetics studies. Twenty different HLA-A, thirtyfive HLA-B and twenty-two HLA-C class I alleles were detected; twenty-seven different HLA-DRB1, fourteen HLA-DQB1 and twelve HLA-DQA1 class II alleles were found. Most frequent extended HLA haplotypes are also depicted. People are present in this area since prehistoric ages according to archaeological studies; the "Out of Africa" eastern migration may have affected the present day population composition.

Research paper thumbnail of Major Histocompatibility Complex Allele Persistence in Eurasia and America in the Genus Carduelis (Spinus) During Million Years

The Open Ornithology Journal, 2017

Introduction:GenusCarduelis(Fringillidaefamily) includes goldfinches, siskins, redpolls, greenfin... more Introduction:GenusCarduelis(Fringillidaefamily) includes goldfinches, siskins, redpolls, greenfinches and crossbills. Many of the species classified within this genus and other related genera have been grouped by using molecular systematics and the mitochondrial cytochrome b (mt cyt b) gene. According to this, the Eurasian siskin (C. spinus)is the only one extant direct ancestor of several North American finches; North American / South American radiations may have been originated by Eurasian siskin (or extinct relative). In the present work, we aim to perform a study of transpecies and transcontinental analyses of MHC (Major Histocompatibility Complex) Class I alleles in several genusCarduelis/Spinusspecies in order to draw evolutionary conclusions in several wild bird species belonging to the genusCarduelis / Spinus.Materials and Methods:Blood was taken from worldwide wild bird species. Passerine phylogeny was done after analysing mtDNA with Maximun Likelihood and Bayesian dendrogr...

Research paper thumbnail of Programmed Cell Death 1 and Helios Distinguish TCR-αβ+ Double-Negative (CD4-CD8-) T Cells That Derive from Self-Reactive CD8 T Cells

Journal of immunology (Baltimore, Md. : 1950), Jan 30, 2015

TCR-αβ(+) double-negative (DN; CD4(-)CD8(-)) T cells represent a poorly understood cellular subse... more TCR-αβ(+) double-negative (DN; CD4(-)CD8(-)) T cells represent a poorly understood cellular subset suggested to contribute to the pathogenesis of the autoimmune disease systemic lupus erythematosus. DN T cells have been proposed to derive from CD8(+) cells. However, the conditions that govern the loss of CD8 expression after Ag encounter are unknown. In this study, we tracked the fate of CD8 T cells from transgenic TCR mice exposed to their cognate Ags as self or in the context of infection. We demonstrate that CD8 T cells lose CD8 expression and become DN only when cognate Ag is sensed as self. This process is restricted to tissues where the Ag is present. We also show that DN T cells derived from self-reactive CD8 cells express the inhibitory molecules PD-1 and Helios. These molecules identify a subset of DN T cells in normal mice. A similar population expands when CD8 T cells from repertoires enriched in self-reactive cells (Aire-deficient) are transferred into cognate hosts. Col...

Research paper thumbnail of Cyclic Expression of HLA Class I and II Molecules on the Surface of Purified Human Spermatozoa and Their Control by Serum Inhibin B Levels

Biology of Reproduction, 1999

HLA class I and class II expression was analyzed weekly by cytofluorometry on spermatozoa samples... more HLA class I and class II expression was analyzed weekly by cytofluorometry on spermatozoa samples from four donors during a 15-wk trial. On the same day that semen samples were studied, and to analyze whether this expression was hormonecontrolled, serum levels of testosterone, LH, FSH, inhibin B, activin, and pro-␣C on the one hand, and seminal plasma levels of inhibin B, activin, and ␣-inhibin on the other, were also measured. Inhibin B and related peptides were quantitated using a novel two-site assay with monoclonal antibodies to the ␣ and ␤ subunits of inhibin. Our results showed that HLA class I and class II molecules were expressed on the spermatozoa's surface, following a cyclic pattern, and that there was a simultaneous and coordinated expression of both types of molecules (r ‫؍‬ 0.801, P Ͻ 0.0001). Furthermore, when the expression of these molecules was plotted against the different hormone levels, serum inhibin B showed a clear inverse correlation with HLA class I (r ‫؍‬ Ϫ0.612, P Ͻ 0.0001) and class II (r ‫؍‬ Ϫ0.534, P Ͻ 0.0001). This finding reveals unexpected functions of inhibin B, which may be relevant in the fertilization process and on male fertility control.

Research paper thumbnail of HLA-G: Too Much or Too Little? Role in Cancer and Autoimmune Disease

Frontiers in Immunology, 2022

HLA-G is a non-classical HLA class I molecule with immunomodulatory properties. It was initially ... more HLA-G is a non-classical HLA class I molecule with immunomodulatory properties. It was initially described at the maternal-fetal interface, and it was later found that this molecule was constitutively expressed on certain immuneprivileged tissues, such as cornea, endothelial and erythroid precursors, and thymus. The immunosuppressive effect of HLA-G is exerted through the interaction with its cognate receptors, expressed on immunocompetent cells, like ILT2, expressed on NK, B, T cells and APCs; ILT4, on APCs; KIR, found on the surface of NK cells; and finally, the co-receptor CD8. Because of these immunomodulatory functions, HLA-G has been involved in several processes, amongst which organ transplantation, viral infections, cancer progression, and autoimmunity. HLA-G neo-expression on tumors has been recently described in several types of malignancies. In fact, tumor progression is tightly linked to the presence of the molecule, as it exerts its tolerogenic function, inhibiting the ...

Research paper thumbnail of Origin of Azeris (Iran) according to HLA genes

International Journal of Modern Anthropology, 2017

Azeris from Iran North West provinces (Tabriz city) have been studied for HLA alleles. A total of... more Azeris from Iran North West provinces (Tabriz city) have been studied for HLA alleles. A total of 8.902 HLA-bearing chromosomes (Chr 6) have been used for comparing their relatedness with other Middle East, Caucasus, Mediterranean and Central Asia populations. Mediterranean, Central Asian and Caucasus extended HLA haplotypes were found, i.e.: A*24:02-B*35:01-DBR1*11:01-DBQ1*03:01 and A*01:02-B*08:01-DRB1*03:01-DQB1*02:01. Genetic distances, Neighbour Joining and Correspondence analyses also showed that Azeris were close to Kurds, who have shown a closer Mediterranean/Caucasus HLA profile, and Gorgan (Turkmen) who have shown a closer Central Asia profile, as expected. It is shown that three different Iranian populations according to Language, History and Geography: Gorgans, Kurds and Azeris are genetically close. In fact, old Azeri language (Adari) was an Iranian language and not a Turkic one, which they nowadays speak. Also, present study does not support "Aryan" invasion from the East in accordance with many other previous studies. Finally, our results are useful for establishing Preventive Medicine programs in Transplantation and HLA and Pharmacogenomics/Disease linkage.

Research paper thumbnail of A Reliable and Standardizable Differential PCR and qPCR Methodology Assesses HER2 Gene Amplification in Gastric Cancer

Biology, 2021

Simple Summary Patients with gastric cancer may present variations in the copy number of the HER2... more Simple Summary Patients with gastric cancer may present variations in the copy number of the HER2 gene in their primary tumors. The techniques used to detect these variations and HER2 overexpression render false positive and negative results with high frequency, and robust methodologies are required to assess this amplification and confidently select patients who may benefit from HER2-specific monoclonal antibody-based therapies. We addressed this issue by molecular biology techniques using DNA samples from tumor or distal tissue of gastric cancer patients. The HER2 and a control (IFNG) gene were subjected to differential (diffPCR) and quantitative PCR (qPCR). A cut-off point above which patients can be deemed positive was set based on the HER2/IFNG ratio, achieved using DNA from 30 healthy donors. Both, diffPCR and qPCR, identified the presence of somatic HER2 amplifications in 25% of patients in DNA from tumoral tissue, but not distal, paired tissue samples. Immunohistochemistry a...

Research paper thumbnail of HLA genes in Chimila Amerindians (Colombia), the Peopling of America and Medical implications

International Journal of Modern Anthropology, 2016

Our aim is to study the HLA-A, -B, -C, -DRB1 and -DQB1 gene frequencies in the Chimila Amerindian... more Our aim is to study the HLA-A, -B, -C, -DRB1 and -DQB1 gene frequencies in the Chimila Amerindian (Colombia) ethnic group. Results are compared with other World populations in order to obtain information about Chimila and Amerindian Health promotion, Amerindian origins and America peopling. Written consent was obtained from Chimila subjects to be included in this study. Peripheral blood was drawn and HLA DNA genotyping was carried out by standard methods. Analyses of Chimila relatedness with other Amerindians and worldwide populations was performed with a standard NJ dendrogram and correspondence analyses methodology. Chimila HLA gene profile showed to be related to that of other Amerindians groups. New complete HLA extended haplotypes were obtained. Some of them are described for the first time. Also, specific genealogical comparisons were done between Chimila Amerindians and Pacific Islanders by using specific HLA alleles. Our conclusions are: 1) These new data and HLA extended ha...

Research paper thumbnail of Kurds HLA Genes: Its Implications in Transplantation and Pharmacogenomics

Open Medicine Journal, 2015

HLA genes (class I and II) have been studied in a Kurd population from Iran (North West towns of ... more HLA genes (class I and II) have been studied in a Kurd population from Iran (North West towns of Saqqez and Baneh, close to Irak border). Kurds speak an Iranian language. HLA Kurd profile has been compared with those of Central Asians, Siberians, Mediterraneans and other worldwide populations; a total of 7746 chromosomes were used for computer comparisons. Both Neighbor-joining and correspondence genetic analyses place Kurds in the Mediterranean population cluster, close to Iranians, Europeans and Caucasus populations (Svan and Georgian). New extended HLA haplotypes are described, being A*02:01-B*35:01-DRB1*01:01-DQB1*05:01 and A*24:02-B*18:09-DRB1*11:01- DQB1*03:01 the most frequent ones; other Kurd extended haplotypes are also found in Azeris and Palestinians. This research work may be useful for: 1) future Iranian Kurds transplantation regional programs, 2) HLA pharmacogenomics in order to practise a preventive Medicine and drug side effects, and 3) Epidemiology of HLA-associated...

Research paper thumbnail of HLA-G in Amerindians: Epidemiology and Worldwide Population Comparison

Open Medicine Journal, 2018

Background:HLA-G molecules are immunosuppressive and avoid fetal rejection by giving negative sig... more Background:HLA-G molecules are immunosuppressive and avoid fetal rejection by giving negative signals to maternal immune system from fetal trophoblast cell surface. HLA-G genes have been associated to different pathologies: Spontaneous abortions, autoimmunity, tumor progression, transplant rejection and infection. In addition, different World populations show remarkable different HLA-G allele frequencies in the allele that does not produce a full HLA-G molecule (HLA-G*05N); this allele is almost absent in studied Amerindians.Objectives:The aim is to study HLA-A.-B,-DRB1 and –G alleles and extended haplotypes in Amerindians for the first time. This may be useful to asses HLA-G epidemiology, association to disease and Preventive Medicine in Amerindians.Methods:HLA-A,-B and -DRB1 have been typed by using standard automatic protocols. HLA-G alleles have been detected by direct HLA-G exon 2, exon 3 and exon 4 DNA sequencing. Computer calculations have been done by specific standard metho...

Research paper thumbnail of Hla in colombia wayu from guajira peninsula amerindians: pacific ocean relationships

Research paper thumbnail of Hla in uros from peru titikaka lake uros: tiwanaku, easter and pacific islanders

Research paper thumbnail of The first free Africans in America: HLA study in San Basilio de Palenque (Colombia)

Human immunology, 2018

Original San Basilio de Palenque population (North Colombia) fled from Spanish traders that carri... more Original San Basilio de Palenque population (North Colombia) fled from Spanish traders that carried them as slaves and they funded in nearby Maria Mountains a fortified town (Palenque). They started helping new Africans brought as slaves to flee and join them. Most of them spoke a Bantu-Congo language and nowadays they speak the only one extant Bantu-Spanish Creole language. Spanish Crown was forced to issue a decree declaring them free (1691 CE), more than 100 years before than Haiti Republic existed. HLA-A, -B, -DRB1 and -DQB1 alleles were studied and further computer procedures were performed with Arlequin 3.5 software. No Amerindian or Europeans gene flow to this population was found. However, three specific HLA extended haplotypes are found in this population, which may reflect an isolation from other Africans or Afro-Americans also. This may be due to the maintenance of their own African culture, and even their unique Creole language.

Research paper thumbnail of HLA genes in Atlantic Celtic populations: are Celts Iberians?

International Journal of Modern Anthropology, 2017

Atlantic Europe populations were analyzed with HLA genes in order to establish their relationship... more Atlantic Europe populations were analyzed with HLA genes in order to establish their relationship among themselves and with other populations. Standard genetic and statistical software analyses were used. Celtic populations (British Isles and French Bretons) have genetically been found close together: Irish, Welsh, Orkney Islanders (Scottish), French Bretons, Galicians, Spanish Basques, Portuguese, cluster together in DA genetic distances, correspondence analysis and Neighbour Joining dendrograms. Genetics have been shown by itself not suffice to determine populations migration/relatedness. Aristotle and Herodotus placed Celts in Iberia and R1b chromosome Y marker is high in Iberia and all Celtic European populations above mentioned (probably stemming from Iberian Ice refugee after Last Glaciation) and Ancient Celt language (Gaelic) is being translated from Iberian-Tartesian language: these suggest that Celts and Iberians, so named by Classic authors, constitute the same population. On the other hand, a) R1b gene analysis of Canary Islands ancient inhabitants (Guanches), b) abundant Iberian scripts are also found in Canary Islands, c) a established North Africa/Iberia ancient gene flow, and d) no evidence of demic diffusion from eastern to western Mediterranean according to human ancient skeleton studies is noticed in Mesolithic/Neolithic transition: these facts suggest that ancient Canary Islanders may be included within the Iberian/Celtic population. Our conclusions are that: 1) Celts are concentrated in Atlantic Europe, 2) Iberians and Celts mentioned by classic authors most probably refer to the same population living in Iberian Peninsula (Spain/Portugal); in addition, North African Berbers and ancient Canary Islanders also belong to this group 3) Postulated farmers demic diffusion in a East to West Mediterranean direction never existed.

Research paper thumbnail of Origin of Ancient Canary Islanders Guanches: presence of Atlantic/Iberian HLA and Y chromosome genes and Ancient Iberian language

International Journal of Modern Anthropology, 2015

First Canary Islands (Spain) Inhabitants ("Guanches") origin has been much debated. Lately, it ha... more First Canary Islands (Spain) Inhabitants ("Guanches") origin has been much debated. Lately, it has come popular the simplistic theory that they came from North Africa. In the present paper, we conclude that not only North Africans but also Iberian/Atlantic Europeans (and possibly others) must have been first Canarians. Debate whether North Africans or Iberians were the first "Guanches" is artificial since Iberian Peninsula-North African genes flow in ancient times was abundant and Iberians share a great part of genetic profile with North Africans. New genetic (HLA) and linguistic data shown in the present paper is conjointly analyzed with early anthropological data; at least two "Guanches" anthropological types existed. In addition, a correct interpretation of R1b Y chromosome high frequency in Atlantic Europe (Ireland, British Isles, North Spain and Portugal), which is also found in Canary Islands (13.3%) supports that Atlantic/Europeans are among Canary Islands First Inhabitants. Present paper HLA genes partial data and presence of abundant old Iberian language scripts (which show an easy translation proposal by using Basque language) suggest that a present day dogma of a hypothetically North African single origin should be changed. Both Atlantic/Europeans and North Africans must have been in the origin of Canary Islands First Inhabitants.